Amine metabolites in cerebrospinal fluid (CSF) are studied in patients to assess neurochemical alterations which may be associated with clinical diagnoses (particularly affective illness, schizophrenia, and alcoholism), biological subgroups, or drug treatment. Probenecid, which inhibits the removal of the metabolites from CSF into the blood, is administered as part of these studies. Sources of variance have been a major focus of study; multivariate statistics are employed to examine these identified sources of variance, including age, sex, activity, and CSF probenecid levels. Fluorometric and mass spectrometric techniques for measureming acid metabolites have been compared. Several studies demonstrate the use of pretreatment CSF metabolite values in predicting drug response to neuroleptics, piribedil, and tricyclic antidepressants. CSF dopamine-beta-hydroxylase levels are similar across diagnostic groups, but show a state-dependent decrease in mania and may be altered by several drugs. Cyclic-AMP levels are similar in mania, depression, and neurological controls. Abstinent alcoholics show decreased 5HIAA levels compared with controls and alcoholics shortly post-intoxication, suggesting interactions between alcoholism and serotonergic activity. BIBLIOGRAPHIC REFERENCES: Jimerson, D.C., Post, R.M. and Goodwin, F.K.: Antidepressant Treatments and Alterations in Central Serotonin Turnover in Affective Illness. In Cohen, M.M. (Ed.): Monographs in Neural Sciences. Basal, Switzerland, S. Karger AG, 1976, pp. 15-22. Kopin, K.J., Kaufman, S., Viveros, H., Jacobowitz, D., Lake, C., Ziegler, M., Lovenberg, W.M. and Goodwin, F.K.: Dopamine-beta-hydroxylase: Basic and Clinical Studies. Ann. Int. Med. 85:211-223, 1976.